Document Detail


The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype.
MedLine Citation:
PMID:  18843282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The poor prognosis of chronic lymphocytic leukemia (CLL) patients with del (17p) is well established. We analyzed whether mutation of TP53 on the remaining allele adds to the poor prognosis or whether even TP53 mutation alone may be an adverse prognostic factor. We analyzed TP53 mutations in 193 CLL patients by denaturing high performance liquid chromatography in combination with direct DNA sequencing and a TP53 resequencing research microarray. Mutations were correlated to chromosomal aberrations defined by interphase fluorescent in situ hybridization and chromosome banding analyses and to the clinical course of patients. TP53 mutations were detected in 13.5% (26 of 193) of samples, whereas the incidence of del (17p) was 9.3% (18 of 193). TP53 mutations were significantly associated with del (17p) (concordance 94%, P<0.001) and complex cytogenetic abnormalities (concordance 50%, P<0.001). Among 147 patients whose clinical data were available, patients with TP53 abnormalities (n=20) had a significantly decreased time to treatment compared to patients without TP53 aberration (P<0.001). Median time to treatment was short in patients with isolated TP53 mutation (n=6, 2.0 months) and in those with del (17p) (n=14, 21.3 months) as compared to patients without TP53 aberration (n=127, 64.9 months, P<0.001). In multivariate Cox regression analysis, VH status, TP53 mutations and also isolated TP53 mutations independently predicted rapid disease progression.
Authors:
F Dicker; H Herholz; S Schnittger; A Nakao; N Patten; L Wu; W Kern; T Haferlach; C Haferlach
Publication Detail:
Type:  Journal Article     Date:  2008-10-09
Journal Detail:
Title:  Leukemia     Volume:  23     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-14     Completed Date:  2009-02-06     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-24     Citation Subset:  IM    
Affiliation:
MLL Munich Leukemia Laboratory, Munich, Germany. frank.dicker@mll-online.com
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MeSH Terms
Descriptor/Qualifier:
Chromosome Aberrations*
Chromosomes, Human, Pair 17
Disease Progression
Humans
Karyotyping
Leukemia, Lymphocytic, Chronic, B-Cell / epidemiology,  genetics*,  pathology*
Mutation*
Predictive Value of Tests
Prognosis
Sequence Deletion
Tumor Suppressor Protein p53 / genetics*
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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